A Study of High-Grade Serous Ovarian Cancer Origins Implicates the SOX18 Transcription Factor in Tumor Development

Cell Rep. 2019 Dec 10;29(11):3726-3735.e4. doi: 10.1016/j.celrep.2019.10.122.


Fallopian tube secretory epithelial cells (FTSECs) are likely the main precursor cell type of high-grade serous ovarian cancers (HGSOCs), but these tumors may also arise from ovarian surface epithelial cells (OSECs). We profiled global landscapes of gene expression and active chromatin to characterize molecular similarities between OSECs (n = 114), FTSECs (n = 74), and HGSOCs (n = 394). A one-class machine learning algorithm predicts that most HGSOCs derive from FTSECs, with particularly high FTSEC scores in mesenchymal-type HGSOCs (padj < 8 × 10-4). However, a subset of HGSOCs likely derive from OSECs, particularly HGSOCs of the proliferative type (padj < 2 × 10-4), suggesting a dualistic model for HGSOC origins. Super-enhancer (SE) landscapes were also more similar between FTSECs and HGSOCs than between OSECs and HGSOCs (p < 2.2 × 10-16). The SOX18 transcription factor (TF) coincided with a HGSOC-specific SE, and ectopic overexpression of SOX18 in FTSECs caused epithelial-to-mesenchymal transition, indicating that SOX18 plays a role in establishing the mesenchymal signature of fallopian-derived HGSOCs.

Keywords: RNA-seq; SOX18; dual origins; fallopian tube secretory epithelial cell; high-grade serous ovarian cancer; machine learning; one-class logistic regression models; ovarian surface epithelial cell; single-cell RNA-seq; super enhancers; transcription factors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Cell Line
  • Cell Line, Tumor
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Epithelial-Mesenchymal Transition
  • Fallopian Tubes / metabolism
  • Fallopian Tubes / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Machine Learning
  • Middle Aged
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Ovary / metabolism
  • Ovary / pathology
  • RNA-Seq
  • SOXF Transcription Factors / genetics*
  • SOXF Transcription Factors / metabolism
  • Single-Cell Analysis
  • Transcriptome


  • SOX18 protein, human
  • SOXF Transcription Factors